Candida albicans is a commensal that colonizes skin and mucosal surfaces including the oral cavity. The organism is also an agent of opportunistic disease of these surfaces as well as internal disseminated disease. Oral candidiasis is associated with derangements of the oral flora related with the acquisition of microbes by neonates and anti-bacterial therapy, oral prostheses, and host factors such as diabetes mellitus and HIV infection. Oral manifestations include pseudomembraneous candidiasis (thrush) and denture stomatitis. Oropharyngeal infection is virtually an inescapable consequence of AIDS (96 percent patients) and frequently reoccurs. Denture stomatitis may affect 50 percent of complete denture wearers. The organism forms biofilms on mucosa, teeth and oral devices such as dentures, generally in association with oral bacteria. Compared to planktonic cells, organisms in biofilms have characteristics such as reduced susceptibility to antifungal drugs and the presence of an extracellular matrix. This study will test the hypothesis that unique characteristics associated with C. albicans biofilms are the result of altered gene expression in general cellular metabolism as well as bioflim specific gene expression. A model of saliva-coated denture acrylic established in this laboratory will be used. About 230 alterations in general cellular metabolism have been identified in biofilm compared to planktonic cells by exploiting the high homology between Saccharomyces cerevisiae and C. albicans and the commercial availability of gene arrays for S. cerevisiae. In Aim 1 this approach will be applied to examine expression temporally during biofilm formation and to other conditions of biofilm development using C. albicans DNA chips. In Aim 2, expression in in vitro biodiverse models will also be examined to identify genes inherently associated with biofilms as differentiated from those influenced by the biofilm environment. Expression of selected genes from the inherent biofilm expression class will be determined in vivo in organisms recovered from human saliva. Aim 3 will examine the role of biofilm-regulated genes such as TUP1and EFG1 using genetically modified strains.